Modern efforts in medicine and healthy living involve the delivery of personalized care and management to the patient. Due to the high variance inherent in biology, including in diagnostic criteria, treatment, and disease management, often the best solution for one patient is far from ideal for another. Before optimal treatment and healthy living for an individual can be prescribed by medical providers, the first step is collecting information about them; however, to date much of this data collection relies on questionnaires and surveys, diagnostic tests being prohibitively expensive, especially for groups that are not at immediate risk. These sorts of human input are often highly variable as they rely on a patient's ability to recall their past behavior as well as their integrity and embarrassment in admitting certain actions associated with (supposed) unhealthy living.
The cost and accessibility of traditional medical diagnostic instruments can and needs to be improved. Currently, diagnosis of disease can take days to weeks while results are sent off to a laboratory, and many diseases still cannot accurately be detected. Devices capable of quickly and accurately diagnosing multiple conditions could be applied to situations ranging from nutrition and vitamin management in first-world locales to antibiotic and vaccine triage in third-world villages. If created and packaged correctly, such devices could ease the burden on gateway physicians, provide impoverished countries with now inaccessible diagnostic capabilities, protect combatants from biological warfare agents, and increase health care access to the average person.
Lateral flow immunochromatographic assays have been widely adopted for diagnosing various diseases and medical conditions in point-of-care settings. These tests are rapid, simple and produce colorimetric signals that can be interpreted by untrained personnel. Unfortunately in most cases, the data interpretation of lateral flow tests depends on the end users who have to make judgments based on their observations, and therefore the results are largely susceptible to error. In recent years, there has been a desire to enhance the accuracy of the measurements, and/or to obtain quantitative information from the lateral flow tests. One exemplary case where higher accuracy is essential, and the subjectivity in determining the test outcome is inappropriate, is for the testing of controlled substances using the lateral flow tests.
The high demand for quantitative readouts has been reflected well by the increasing number of semi-portable readers on the market for analyzing the lateral flow assays. However the cost and size of these specialized reader systems still remain to be significant, and hamper their widespread adoption for many end consumers. Also, most of the commercial readers for lateral flow tests are only semi-portable and/or require connection to the computer systems to perform the required analysis. For example, the sizes of ESEQuant Lateral Flow Immunoassay Reader (Qiagen, Germany) and SkanMulti (Skannex, Norway) are still relatively bulky and thus are not truly portable. Furthermore, SkanMulti functions only as an imaging system and requires a computer to analyze the acquired data.
One implementation of state-of-the-art diagnostics is as smartphone and/or tablet (i.e., portable computing) accessories where the computational power, read-out, data storage, and connectivity are provided by an existing device. The smartphone has penetrated nearly all aspects of our lives, affecting how we consume media including news and entertainment, how we track our finances and pay for goods and services, and how we monitor our health and fitness. However, for all of the benefits smartphones have provided, there is still little or no direct connection between smartphones and in vivo biochemistry. By enabling a direct link between a smartphone and small molecule detection, monitoring, and tracking, a number of new benefits could be realized in the fields of medicine and healthy living, including, e.g., simple diagnosis of disease and nutrient deficiencies; monitoring and tracking of existing conditions; and social media-enabled healthy living updates, competition, game playing, and mapping.
Moreover, some companies have indeed explored smartphone solutions for reading the lateral flow tests. For example, mReader software (MobileAssay, Colorado, USA) can be installed on smartphone systems and used to analyze the test strip images taken from the smartphone cameras. Although the use of smartphone systems to replace the specialized readers effectively addresses the aforementioned limitations, they do so at the expense of reliable imaging as the images are taken in the open environment whose lighting conditions cannot be accurately controlled.
Suboptimal nutrition is one of the most acute problems facing the developed and developing world today. Worldwide, there are more disability-adjusted life years lost to malnutrition than any other medical condition; it is reported that over 1,000,000 people die every year from vitamin A and zinc deficiencies, and 30% of all cancers are related to poor diet (by comparison genetics and obesity account for only 5% and 10% of all cancers respectively). Optimal pre-natal maternal folic acid levels are well co-related with a reduction in neural tube defects and evidence suggests that fetal brain development is enhanced by docosahexaenoic acid (DHA) intake. Micronutrient (i.e., vitamins and minerals) deficiencies have been tied to dozens of different health conditions including anemia, rickets, scurvy, cardiovascular disease, and cancer. Additionally, recent work has linked vitamin deficiencies to obesity, one of the major challenges facing the current generation.
The Copenhagen Consensus has identified tackling vitamin and micronutrient deficiencies as the most cost-effective intervention to further global development and progress in published reports since 2004. Domestically, the Institute of Medicine has concluded half of older adults in the United States who had hip fractures had serum levels of 25(OH)D less than 12 ng/mL; (25-hydroxyvitamin D [25(OH)D] is considered to be the best indicator of vitamin D; and, that levels below 20 ng/mL are inadequate for bone and overall health. The vast majority of vitamin and micronutrient analysis is done through blood collection via venipuncture, which is then sent away to a centralized laboratory. This analysis is slow, expensive, requires trained personnel, and is not widely available, particularly in resource-limited settings where micronutrient deficiency is most harmful. A combined HPLC-MS method is considered the industry standard for vitamin D testing, however ELISA kits and similar immunoassays are comparable in terms of sensitivity and accuracy, while being better suited for adaption to home use. Since micronutrient deficiencies are not often clinically obvious, these tests are typically done at the insistence of the patient. The fact that so many Americans are vitamin deficient testifies to the fact that the current methodologies are not working.
Salivary cortisol is a routinely used biomarker of stress and related psychological diseases. Commonly, cortisol is elevated in patients who experience a sudden stressor and returns to normal after a period of time whose length is dependent on the strength of the stressor. In patients with chronic stress disorders, such as PTSD, it has been difficult to co-relate absolute levels of cortisol at any given time with the diagnosis of a disorder due to the large number of confounders. A better approach would be to track cortisol, and other biomarkers, over time to look for trends that could be indicative of the onset psychological disease.
Every year hundreds of millions of people suffer from infectious diseases including respiratory infections, HIV/AIDS, diarrheal diseases, tuberculosis, and malaria. The agents that cause these diseases, including bacteria, viruses, fungi, etc., are often easily manageable with proper identification yet routinely go undetected because of the costs and difficulties associated with diagnostic technology. In some cases, such as tuberculosis, identifying the disease rapidly and on location can allow for preventative measures prohibiting the disease from spreading further. In other cases, such as HIV, keeping an acute-eye on antibody levels is critical in tracking the progress of the disease.
Kaposi's sarcoma (KS) is an opportunistic infectious cancer that first became widely known during the acquired immunodeficiency syndrome (AIDS) epidemic of the 1980s. During this time period, the appearance of symptoms of KS, red lesions on the skin, became signs that an individual was infected with human immunodeficiency virus (HIV) and KS itself became known as an AIDS-defining illness. As the battle against AIDS waged on, the introduction of highly active anti-retroviral therapy (HAART) helped reduce KS incidence. Years later, however, HIV infected individuals still contract KS at a higher occurrence than when compared to the pre-AIDS era. Today, KS is the fourth leading cancer in sub-Saharan Africa, and in some countries, such as Uganda, is the most prevalent cancer in men. The root cause of KS is Human herpes virus 8 (HHV-8), more commonly referred to as Kaposi's sarcoma associated herpes virus (KSHV). While the virus is often asymptomatic in healthy individuals, a number of populations, including those immune-compromised by HIV, are vulnerable to its symptoms. The virus is commonly believed to be transmitted through saliva and in some regions rapidly spreads, beginning in childhood affecting large portions of the population, reaching seroprevalence of over 50%. Like other herpes viruses, KSHV can establish a latent infection and remains without causing any disease for the remaining life in most infected hosts, being necessary but not sufficient of KS development.
In the developed world, medical professionals diagnose KS with sufficient accuracy. If typical hematoxylin and eosin (H&E) staining are applied to a KS biopsy section a number of unique features can be observed, including many and large vascular spaces as well as high numbers of spindle cells thought to be of lymphatic endothelial origin. However, due to the existence of similarly presenting diseases, such as bacillary angiomatosis (BA), identification of these features is not sufficient for diagnosis of KS. In modern hospitals this is solved through immunohistochemistry staining for protein markers of KSHV, or through application of PCR for KSHV sequences. However, neither of these techniques is readily adaptable for use in the developing world where KS is most prevalent.
The alarming increase in premature deaths due to heart disease in the developed world has resulted in numerous efforts to make blood cholesterol measurements accessible outside the clinical setting. It is estimated that 60% of adults in the US have high cholesterol (over 200 mg/dl), with 37 million among them having very high cholesterol (over 250 mg/dl). Long-term studies on the effect of serum cholesterol on coronary heart disease mortality indicate that there is a 17% increase in mortality rate for every 20 mg/dl increase in serum cholesterol levels above 210 mg/dl. Monitoring cholesterol levels is important because it can empower people to make lifestyle choices for preventing heart disease later in life. For some people, improving diet and increasing exercise can lower overall cholesterol, but in some cases medication needs to be prescribed. Products such as Cardiochek and Cholestech have been on the market for over a decade; however home cholesterol testing is still not common. A recent study suggested that current cholesterol kit users are interested in easier ways of tracking results and that they would test more frequently if supplies were more affordable. The accuracy of those devices is also a major user concern and has been addressed in several publications.
Finding a solution to the aforementioned challenges and problems directly motivated the development of lab-on-a-chip based point-of-care diagnostics beginning some 15 years ago. The technical vision behind these kinds of systems comprised two parts: a consumable “chip” that contained microfluidics and a biosensor, and a “reader” instrument that interpreted the signal from the chip and provided results to the operator. Since this vision was first put forward, the technology has advanced at an incredible rate to the point where we now have devices that can operate over a million microfluidic valves in parallel, portable PCR machines for pathogen detection, nanosensors that can detect a handful of molecules, and numerous other systems. These developments have significantly reduced the size of the sample required to perform a blood analysis.
Smartphones have the potential of addressing all these issues by eliminating the need for separate test kits. Test strips could be imaged directly on a smartphone and the processed data can be stored for tracking or sent via e-mail directly to a physician. Smartphone accessories for the detection of biomarkers in bodily fluids have been the subject of extensive investigation because they have the potential of greatly decreasing the cost and increasing the availability of heath care in the world.
It is predicted that by 2016 there will be 250 million smartphones in use in the US. A good portion of the complexity required to make and interpret a quantitative in-vitro measurement is already embedded in smartphones, resulting in a paradigm shift in the “razor and blades” model. Put simply, most consumers now already own the expensive part, the “Razor,” in the form of a smartphone; all one needs then is the blades.
The inventors have recognized that quantitative analyses of bodily fluids like sweat, saliva, urine, blood, and others would provide a deep wealth of physiological information. The inventors have also recognized that, in addition to mobile, point-of-collection devices and methods that address the challenges outlined above, there is an intense need for the ability to obtain accurate, consistent, and standardized quantitative measurements and, independent of the smartphone platform being used, the benefits and advantages of which would contribute to better quality of life.
These and other objects, benefits, and advantages provided by the solutions enabled by the embodied invention will be described in detail below with reference to the accompanying figures and as set forth in the appended claims.